[Immunogenicity of experimentally combined hepatitis A and hepatitis E vaccine at different dosage ratio]

To evaluate the immunogenicity of experimentally combined hepatitis A and hepatitis E (cHA+E) vaccine and analyze the interactions between the two antigenic components in vaccine.

Nine different dosage ratio of the cHA+E vaccine, A500 + E200, A500 + E100, A500 + E50, A250 + E200, A250 + E100, A250 + E50, A125 + E200, A125 + E100 and A125 + E50 (U+mg)/L, was prepared from an inactivated hepatitis A (HA) vaccine and a hepatitis E (HE) vaccine. 120 mice were immunized with the cHA+E vaccine, HA vaccine and HE vaccine alone in different doses, respectively. Mice were bled before immunization and 2, 4, 6, 8, 10, 12 and 14 weeks post immunization. Specific antibodies against hepatitis A and E viruses were detected by ELISA and neutralization assay.

After immunization with different dosages of cHA+E vaccine, all animals developed hepatitis A virus antibody (anti-HAV) and hepatitis E virus antibody (anti-HEV). Anti-HAV responses increased with the concentration of the HA vaccine component in the cHA+E vaccine. Anti-HAV neutralizing antibody titers reached 1:1 024 when mice were immunized with cHA+E vaccine prepared from higher dosage (500 U/mL) of the HA vaccine. The titers only reached 1:512 when lower dosages (250 and 125 U/mL) of HA vaccine were applied. However, different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine developed no effects on the production of anti-HAV neutralizing antibody. In addition, comparing with the single HE vaccine, the cHA+E vaccine induced higher level of anti-HEV response. The anti-HEV level increased with the concentration of HA vaccine component in the cHA+E vaccine. However, there was no obvious relationship between the anti-HEV levels and the different dosages (200, 100 and 50 mg/L) of the HE vaccine component in the cHA+E vaccine. Immune sera elicited by the cHA+E vaccine neutralized HEV infectivity when detected by an in vitro RT-nPCR-based HEV neutralization assay.

In cHA+E vaccine, the HA vaccine component can increase the immunogenicity of the HE vaccine component, and the HE vaccine component plays no adverse effects on the immunogenicity of the HA vaccine component.